Vaccines have depended to a great degree on substantially intact organisms. By using substantially intact organisms which were attenuated or killed, it was hoped that one could reproduce the native pathogen conformation and immune response, so that the immune system would be activated and create memory cells without having to be subjected to the pathogenicity of the virulent organism. For some diseases this has proven quite satisfactory. However, in other cases, the method has failed for a variety of reasons.
When using live, attenuated organisms, there is always the concern that the attenuated organism may be restored to virulency. While in individual cases, the probability is low, where one is doing mass vaccinations, having a pathogenic organism greatly increases the likelihood of infection among a few patients. In other instances, toxins may be involved, which to varying degrees in individuals may result in disease symptoms. In these situations one must weigh the beneficial effects for the major population against the adverse effects to individuals. The situation applies to whooping cough, caused by the organism Bordetella pertussis. The pertussis toxin is an enzyme which catalyzes ADP-ribosylation. The toxin has a broad spectrum of adverse effects on the host. Thus in the case of the vaccine, it is not sufficient that the organism be inactivated since the intact toxin can provide for life-threatening results.
Based on various investigations, it is believed today that different individuals may respond to different portions of an antigen. In the case of antigen-presenting cells such as B-cells, one protein may bind to the surface immunoglobulin and another protein may bind to an MHC antigen and be presented to and recognized by T-cells. Thus in humans, depending on the HLA-type, the response to an antigen may vary between different individuals, and some individuals may not mount a strong immmune response to the antigen.
There is therefore substantial interest in being able to develop vaccines which will have broad application throughout the population without the uncertainties of using either attenuated or killed intact pathogens, while providing for a strong immune response in all or substantially all individuals to be vaccinated.